Alterations in thyroid hormones and/or TRH systems have been implicated in the expression of affective disorders. In addition, thyroid hormones and TRH influence psychotropic drug therapy and several drugs used in the treatment of affective disorders alter hypothalamic/pituitary/thyroid axis activity. Evidence accumulated over the past decade points to a neural role for thyroid hormones in the adult brain. TRH has been hypothesized to play a role in the regulation of CNS activity. Thyroid hormones are actively taken up into brain tissue where they are localized within discrete brain regions. Many of these regions which accumulate thyroid hormones also contain high concentrations of TRH neurons and/or receptors. The interrelationship of central thyroid hormones and TRH systems in the modulation of CNS activity is unknown. If the activity of central iodothyronines influences the production and/or utilization of TRH, then both of these hormones might be coordinately involved in the expression of affective illness. These ongoing studies are aimed at defining the nature of the interaction between central thyroid hormones and TRH systems. The activity of TRH systems are being assessed by measurements of TRH biosynthesis using cDNA/RNA hybridization methods and TRH receptor number and affinity by quantitative autoradiography. The results of these studies will provide information concerning the influence of thyroid hormones on the activity of TRH systems. They will serve as the foundation for studies of the possible interaction of thyroid hormones and TRH in the modulation of affective disease.